Methylphenidate increases creatine kinase activity in the brain of young and adult rats.
OBJECTIVE
The high prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) and the increased therapeutic use of methylphenidate (MPH) raise some concerns regarding its long-term side effects and safety profile. Considering that MPH effects on brain metabolism are poorly known and that creatine kinase (CK) plays an important role in cell energy homeostasis, we evaluated CK activity in the brain of young and adult rats following acute (one injection) or chronic (28 days) administration of MPH.


METHODS
MPH was acutely or chronically administered to young and adult rats. For acute administration, a single injection of MPH was given to rats on postnatal day (PD) 25 or PD 60, in the young and adult groups, respectively. For chronic administration, MPH injections were given to young rats starting at PD 25 once daily for 28 days (last injection at PD 53). In adult rats, the same regimen was performed starting at PD 60 (last injection at PD 88). CK activity was measured in brain homogenates.


RESULTS
Our results showed that MPH acute administration increased the enzyme in prefrontal cortex, hippocampus, striatum and cerebral cortex, but not cerebellum of young and adult rats. Chronic administration of MPH also increased CK activity in these brain regions, as well as the cerebellum, in young and adult rats. The highest dose (10.0 mg/kg) presented more pronouncing effects.


CONCLUSIONS
The present findings suggest that acute or chronic exposure to MPH increased CK activity, an enzyme involved in energy homeostasis, in the brain of young and adult rats.
Scaini
Giselli
G
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Fagundes
Ana O
AO
Rezin
Gislaine T
GT
Gomes
Karin M
KM
Zugno
Alexandra I
AI
Quevedo
João
J
Streck
Emilio L
EL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D003402:Creatine Kinase / Q000378:metabolism*; D004334:Drug Administration Schedule; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D003402:Creatine Kinase